It is known that many physiologically active linear peptides do not have uniform conformation in solutions and have poor stability to protease. In order to solve these problems, cyclic peptide derivatives which are intended to have fixed conformation have been proposed.
For instance, cyclic peptides of somatostatin have been reported to have an elevated activity and improved stability as compared with the corresponding linear peptides [Nature, 292, 55 (1981)].
Cyclic peptides derived from peptides portions of gallanin have stabilized conformation, but it has been reported that their activity is noticeably lowered [Int. J. Peptide Protein Res., 38, 267 (1991)].
It is known that a peptide having a sequence of Arg-Gly-Asp (RGD) participates in the binding of integrin. Disorders caused by adhesion of cells' via integrin include platelet thrombosis, vascular re-obstruction, osteoporosis, inflammation, etc. Peptides which inhibit the binding of integrin through RGD sequence are useful as medicines for treating the disorders [Endocrinology, 132 (3), 1411 (1993); J. Cell Biology, 111, 1713 (1990); J. Bone and Mineral Research, 8, 239 (1993); Science, 233, 467 (1986); Tissue Culture, 15 (14), 486 (1989); Br. J. Cancer, 60, 722 (1989); Jpn. J Cancer Res., 81, 668 (1990); Cell, 65, 359 (1991); Science, 260, 906 (1993); Experimental Medicine, 10 (11), 76 (1992)].
Regarding RGD-related peptides, sequences of portions of human fibronectin mentioned below are known [Nature 350, 66 (1991)]:                H-Val-Thr-Gly-Arg-Gly-Asp-Ser-Pro-OH (SEQ ID NO:1)        H-Val-Tyr-Ala-Val-Thr-Gly-Arg-Gly-Asp-Ser-Pro-Ala-OH (SEQ ID NO:2)        
Regarding RGD-related peptides, a cyclic peptide, cyclic (-Arg-Gly-Asp-D-Phe-Val-), has been reported to have an elevated activity of from 20 to 100 times the activity of Gly-Arg-Gly-Asp-Ser [FEBS Lett. 291, 50 (1991)].
Naturally occurring snake venom peptides are known having a Cys-Cys cyclic structure, trigramin (72 residues) [Biochemistry, 28, 661 (1989)], albolarin (73 residues), flavoridin (65 residues) [Biochemistry, 30, 5225 (1991)], etc. These have an activity of about, 1000 times higher than the activity of Gly-Arg-Gly-Asp-Ser (SEQ ID NO:3). In addition, the following cyclic peptides having a structure derived from these are known (JP-A-5-70364): wherein X represents H, or at least one amino acid residue; Y represents OH, or at least one amino acid residue; R represents the same or a different amino acid residue.
In addition, there are various reports referring to cyclic Arg-Gly-Asp-related peptides [Biochem. Biophys. Res. Commun., 177, 74 (1991); Angew. Chem., 104, 341 (1992); Tetrahedron Lett., 33, 1479 (1992); J. Chem. Soc. Perkin Trans., 2, 601 (1991); Cancer Lett., 65, 259 (1992); J. Med. Chem., 35, 3962 (1992); U.S. Pat. No. 4,683,291; WO89-05150; EP-A-0319506; EP-A-0341915; JP-A-4-506803].
It is known that the farnesylating modification of proteins is catalyzed by farnesyltransferase (FTase). Ras proteins that are activated by the modification participate in controlling the differentiation and the growth of cells. It is believed that if the control is disrupted by a mutation, cells undergo transformation and cancer results. Therefore, substances capable of inhibiting the farnesylation of proteins are useful as carcinostatics.
FTase is an enzyme which specifically recognizes an amino acid sequence comprising the C-terminal four residues of a protein, C-a1-a2-X (where C is a cysteine residue; a1 and a2 each are an aliphatic amino acid residue; and X is an amino acid residue), while acting to transfer the farnesyl group of farnesylpyrophosphoric acid into a cysteine residue.
Many peptides having the C-terminal sequence C-a1-a2-X which is recognized by FTase have been reported to be FTase inhibitors. [Cell, 62, 81 (1990); J. Biol. Chem., 265, 14701 (1990); ibid., 266, 15575 (1991); Proc. Natl. Acad. Sci. USA, 88, 732 (1991); ibid., 89, 8313 (1992); JP-A-6-157589 and JP-A-6-157590; Cell, 57, 1167 (1989); Protein, Nucleic Acid and Enzyme, 38, 1695 (1993)].
For example, peptides having the following sequences are known:                H-Cys-Met-Gly-Leu-Pro-Cys-Val-Val-Met-OH (SEQ ID NO:5)[Cell 57, 1167 (1989); Protein Nucleic Acid and Enzyme, 38, 1695 (1993)]; and        H-Ser-Ser-Gly-Cys-Val-Leu-Ser-OH (SEQ ID NO:6)[J. Biol. Chem., 265, 14701 (1990)].        
In addition, analogues to these peptides have also been reported [J. Biol. Chem., 268, 18145 (1993); ibid., 268, 20695 (1993); ibid., 269, 12410 (1994); Science, 260, 1934 (1993); Bio. Med. Chem. Lett., 4, 887 (1994)].
Cyclic derivatives of FTase-inhibiting peptides have been reported to have an increased activity of from 10 to 50 times the activity of the original peptides [Science, 260, 1937 (1993)].
It is known that a natriuretic peptide derived from human atria (hereinafter referred to as ANP) expresses its physiological activity via two receptors GC-A and GC-B [Nature, 338, 78 (1989); Cell, 58, 1155 (1989); Nature, 341, 68 (1989)], and it is also known that ANP has diuretic activity and blood pressure-depressing activity as the main activities [Life Sci., 28, 89 (1981); Biochem. Biophys. Res. Commun., 118, 131 (1984); J. Clin. Invest., 84, 145 (1989)]. Therefore, ANP-agonists are useful as blood pressure-depressing diuretics.
In addition to the above-mentioned receptors, C-receptors which have no intracellular signal transmission domain are known. Such C-receptors do not exhibit their physiological activity even when ANP binds thereto, and it is considered that these act as clearance receptors for ANP [Science,. 238, 675 (1987); Cellular Signalling, 6, 125 (1994)]. Accordingly, it is believed that substances binding to C-receptors can increase the ANP concentration in blood by inhibiting the clearance for ANP and therefore exhibit the same effect as ANP agonists.
Many C-receptor-binding peptides have been reported, including peptide portions of ANP and derivatives thereof [“Peptide Regulation of Cardiovascular Function”, pp. 65-77, Ed., Imura, Matuo and Masaki, Academic Press (1991); Eur. J. Pharmacol., 147, 49 (1988); J. Med. Chem., 32, 869 (1989); J. Biol. Chem., 2, 10989 (1.988); JP-A-3-50348; Int. J. Peptide Protein Res., 43, 332 (1994); WO94/14839; WO94/14840.
For example, in “Peptide Regulation of Cardiovascular Function”, pp. 65-77, Ed., Imura, Matuo and Masaki, Academic Press (1991), a peptide having the following sequence corresponding to amino acids 8-15 of human ANP is disclosed:                H-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-NH2 (SEQ ID NO:7), anda derivative of a peptide having a sequence corresponding to amino acids 7-18 of human ANP, wherein the 7th and 18th amino acids are substituted by alanines:        H-Ala-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Ala-NH2 (SEQ ID NO:8).        
Cyclic derivatives of the peptides portions of ANP have been reported to have an increased receptor-binding activity of about two times the activity of the peptides portions of ANP [J. Med. Chem., 32, 67 (1989)].
Bradykinin (hereinafter referred to as BK) is an endogenous peptide having various physiological activities of, for example, vasoconstriction, bronchoconstriction, inflammatory reaction, algesiogenic transmission, etc., and this is considered to be one substance participating in the conditions of various disorders such as hypertension, inflammation, pain, asthma, septicemia, etc. Therefore, substances that are antagonistic to BK and inhibit the activities of BK are expected to be useful for treating and preventing these disorders.
There have been many reports that make reference to BK-antagonistic peptides [“Small peptides, Chemistry, Biology and Clinical Studies”, pp. 83-102, Ed., A. S. Dutta, Elsevier (1993); “Peptides, Chemistry, Structure and Biology (Proceedings of the 13th American Peptide Symposium)”, pp. 349-352, 353-355 and 449-451, Ed., Hodges and Smith, ESCOM (1994); Bio. Med. Chem. Lett., 4, 781 (1994)). For example, a BK-antagonistic peptide having the following sequence is known:                H-D-Arg-Arg-Pro-Hyp-Gly-Phe-Cys-D-Phe-Leu-Arg-OH (SEQ ID NO:72)wherein Hyp represents a hydroxyproline [“Peptides, Chemistry, Structure and Biology (Proceedings of the 13th American Peptide Symposium)”, pp. 349-352, 353-355 and 449-451, Ed., Hodges and Smith, ESCOM (1994)].        
Cyclic BK-antagonistic peptides have been reported [“Peptides, Chemistry, Structure and Biology (Proceedings of the 13th American Peptide; Symposium)”, pp. 381-383, 547-549, 550-552 and 687-689, Ed., Hodges and Smith, ESCOM (1994)].
However, there is no report referring to novel peptides provided by the present invention.